Tackling slow set up times for Paediatric Clinical Trials

The ECMC Network supports the delivery of early phase oncology trials in the UK, including complex innovative design and paediatric studies. Analysis of our portfolio shows that it takes on average 41 days longer to set up a paediatric trial compared to adult trials, and anecdotal reports from academic and commercial sponsors cite paediatric trials opening in the UK up to 12 months after their European counterparts.  
 
We set out to investigate the key challenges in paediatric early phase trial set-up. In May 2020, we published a report outlining major causes of delay and opportunities to streamline processes in order to bring novel treatments to patients, sooner. 
 
 
What have we done so far to address these challenges? 
 
In light of the disruption to cancer research and trials caused by the COVID-19 pandemic, the ECMC Paediatric Network is seeking to address some of the issues identified in our report, focussing on the following two areas: 
 

1. Developing standard of care consensus guidance for paediatric indications. 

 
Challenge: Costing paediatric trials can prove challenging due to the complexity of the disease and a lack of consensus 'standard of care' for relapsed patients, resulting in underfunded trials and contract delays due to difficulty negotiating excess treatment costs.  
 
Action: The Network agreed to develop a consensus document that outlines the minimum standard of care investigations for relapsed paediatric cancer patients, to support with the design of early phase trials and identification of excess research costs. 
 
Output: Starting with Neuroblastoma as an initial pilot, ECMC Paediatric Leads worked with the NCRI Neuroblastoma subgroup to draft this consensus document for UK clinical investigators. The pilot consensus document has been drafted to be shared on the CCLG website as a resource for paediatric oncologists and clinical investigators to inform relapsed patients’ care and early phase clinical trial design. The Network plans to evaluate its use in simplifying academic trial costing and design and will roll out the pilot to other cancer types.  
 
2. Collating experiences of research ethics review for paediatric trials. 
 

Challenge: Commercial and academic sponsors cited variable experiences of ethics review for paediatric early phases studies. Feedback received from the Research Ethics Committee (REC) could lack awareness of the paediatric research setting, leading to unnecessary amendments and delays.  

 
Action: To identify potential solutions, further data was required to understand the specific challenges faced by trial sponsors and investigators when taking these trials through RECs. Data was collected via survey and through discussions with the ECMC Paediatric Strategy Group and ABPI Members. 
 
Output: We produced a report summarising these findings for discussion with the Health Research Authority (HRA), which provided input into their review of ethics services conducted in January 2021, and since then we have continued to work closely together. We are currently supporting their Think Ethics programme by facilitating access to ECMC expertise in early phase, complex, and paediatric studies, to ensure their work packages consider matters raised in our report. 
 
Looking ahead - what next? 
 
In March 2021, as a result of the many learnings from the UK’s rapid clinical response to COVID-19, the UK Government launched its Vision for Clinical Research Delivery. This, and other pilot initiatives launched during 2020-21, significantly changed the landscape within which the original project report and recommendations were developed.  
 
As regulators and clinical research organisations move forward with the implementation of this vision, we will continue to work closely with the key organisations, such as the HRA and NIHR, to raise awareness and address the specific challenges faced in the set-up of early phase, complex innovative design and advanced therapy studies.We plan to:
  • Evaluate the use of the standard of care consensus document and roll out to other paediatric cancer types through the NCRI Childrens Group. 
  • Continue to support the HRA Think Ethics programme.  
  • Launch a Rapid Delivery Programme in partnership with the HRA and MHRA. 
  • Review the National Institute for Health Research (NIHR) Interactive Costing Tool (ICT) and develop guidance for costs associated to Phase I/IIa/ Advanced Therapy Investigational Medicinal Product (ATIMP) studies.  
  • Continue convening our ECMC Operational Leads forum to capture delivery challenges at site for communication with key organisations.  
 
For more information on this project or the ECMC Network, please get in touch at ECMCAdmin@cancer.org.uk.